A study led by the National Research Council (CSIC) has shown that a signaling pathway essential in this process is jointly controlled by Vav2 and Vav3 oncoproteins, enzymes that determine the activation of signaling pathways related to mobility and cell proliferation.
The results of the study, published in the journal PLoS Biology, may provide drug targets aimed at the tumor and other skin diseases such as psoriasis.
"To demonstrate the effect of inactivation of these activators in skin cancer, we used mice genetically engineered to eliminate the expression of proteins and Vav3 Vav2. With this strategy, you want to simulate the effect of the systemic use of inhibitors against these two proteins would have on the initiation and progression of skin tumors and at the same time, assess the side effects that could cause such inhibition in normal skin tumor, "explains Xosé Bustelo CSIC researcher, Center for Cancer Research of Salamanca, a joint CSIC and the University of Salamanca.
This experimentally demonstrated that the removal of proteins and Vav3 Vav2 caused a significant fall of the induced skin tumors in mice after topical application of various carcinogens. However, mice lacking these two proteins showed no alteration in the normal development of the skin, indicating that the use of inhibitors against Vav3 Vav2 and specifically affect the viability of the tumor cells but not normal cells of patients skin cancer.
During the study it was found that the expression of these two proteins was necessary for the survival of tumor cells to agents that, like many of the drugs used in chemotherapy cause cell death through the induction of DNA damage. In addition, researchers were able to show that the proteins Vav were also necessary for optimum proliferation of tumor cells and induction of other biological processes, such as local inflammation intratumoral, create an environment that encourages tissue growth and cell survival tumor in a more robust.
Furthermore, the researchers found that proteins Vav mediate largely above all biological processes through activation of a transcriptional program that determines the expression of a wide variety of extracellular factors involved in the survival and proliferation of skin cells tumor and the adjacent normal cell stimulation to tumor cells that promote the creation of tumor niche.
"These experiments indicate that Vav3 Vav2 and play an important role in the initiation and development of skin cancers, to promote cell signaling pathways in cancer cells related to DNA damage cell survival, proliferation and tissue microenvironment modification where such cells grow and develop. Many of these programs are activated protumorigenic other common diseases of the skin, as in the case of psoriasis, "Mauricio Menacho-Marquez, CSIC researcher at the Cancer Research Center of Salamanca.
The investigation also involved researchers from the Center of Molecular Biology "Severo Ochoa" CSIC and the Centre for Energy, Environment and Technology.
Mauricio Menacho-Márquez, Ramón García-Escudero, Virginia Ojeda, Antonio Abad, Pilar Delgado, Clotilde Costa, Sergio Ruiz, Balbino Alarcón, Jesús M. Paramio, and Xosé R. Bustelo. The Rho Exchange Factors Vav2 and Vav3 Favor Skin Tumor Initiation and Promotion by Engaging Extracelular Signaling Loops. PLOS Biology. DOI: 10.1371/journal.pbio.1001615
Picture By →AzaToth (self made based on PDB entry) [Public domain], via Wikimedia Commons